Related Experiment Video

Updated: Mar 10, 2026

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages
08:41

Visualization of Inflammatory Caspases Induced Proximity in Human Monocyte-Derived Macrophages

Published on: April 6, 2022

3.2K

The ASC-c isoform as a modulator of inflammasome activation: Insights into molecular mechanisms and therapeutic

Meenakshi Sharma1, Anthony Waterston1, Christopher J Randolph1

  • 1Department of Bioengineering, School of Engineering, University of California, Merced, California, USA.

The Journal of Biological Chemistry
|March 9, 2026
PubMed

Insights

ASC-c, an inflammasome regulator, interacts with ASC and affects its self-association, inhibiting inflammasome assembly. A peptide derived from ASC-c shows therapeutic potential by targeting ASC for drug design.

Area of Science:

  • Immunology
  • Structural Biology
  • Biochemistry

Background:

  • Inflammasome activation is crucial for immune responses but contributes to chronic inflammatory diseases when dysregulated.
  • The adaptor ASC (Apoptosis-associated speck-like protein containing a CARD) is central to inflammasome assembly through homotypic interactions of its PYD and CARD domains.
  • ASC-c, an ASC isoform, negatively regulates inflammasome activity, but its structural basis and mechanism remain unclear.

Purpose of the Study:

  • To elucidate the structural properties and interaction mechanisms of ASC-c with ASC.
  • To investigate how ASC-c binding influences ASC self-association and inflammasome assembly.
  • To develop and validate a therapeutic peptide targeting ASC based on ASC-c structure.

Main Methods:

  • Nuclear magnetic resonance (NMR) spectroscopy to assess ASC-c structure.
  • Chemical shift perturbation (CSP) analysis to map ASC-c and ASC interactions.
  • Transmission electron microscopy (TEM) and dynamic light scattering (DLS) for polymerization studies.
  • Fluorescence anisotropy and molecular dynamics (MD) simulations for peptide-ASC interaction analysis.
  • Cell-based assays to evaluate inflammasome activation inhibition.

Main Results:

  • ASC-c possesses a folded CARD domain but a distinct two-helix PYD structure, differing from typical Death Domains.
  • ASC-c directly interacts with ASC, influencing ASC self-association and polymerization into heterogeneous filaments.
  • A peptide derived from the ASC-c PYD binds ASC and demonstrates inhibitory effects on inflammasome activation in cell-based assays.
  • MD simulations confirmed the stability of the peptide-ASC complex.

Conclusions:

  • ASC-c's unique structural features and its interaction with ASC modulate inflammasome assembly, offering a regulatory mechanism.
  • The ASC-c derived peptide represents a promising therapeutic strategy for targeting ASC in inflammatory diseases.
  • Understanding ASC-c's role provides insights into inflammasome regulation and potential drug development avenues.
Keywords:
ASC isoformsNMRinflammasomeinflammasome inhibitionpeptide designprotein structureprotein-peptide interactionsprotein-protein interaction

More Related Videos

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages06:52

Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages

Published on: May 21, 2018

11.3K
Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells09:04

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

Published on: May 22, 2014

21.5K

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.5K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.1K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
10.2K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.0K